Myogenic nitric oxide synthase activity in canine lower oesophageal sphincter: morphological and functional evidence

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Abstract
Studies on canine lower oesophageal sphincter (LOS) evaluated the existence and function of a myogenic, nitric oxide synthase (NOS) by use of immunocytochemistry for NOS isozymes, NADPH‐d histochemistry, [3H]‐L‐arginine to [3H]‐L‐citrulline transformation. In addition, functional studies in the muscle bath were performed. Smooth muscle bundles or freshly isolated smooth muscle cells of LOS were NADPH‐d reactive but did not recognize some antibodies against neural, endothelial or inducible NOS. NADPH‐d reactivity and immunoreactivity to a neural NOS antibody were colocalized in LOS enteric nerves. Muscle plasma membrane‐enriched fractions from fresh and cultured LOS cells converted [3H]‐L‐arginine to [3H]‐L‐citrulline; activity was mostly Ca2+/calmodulin‐dependent. N‐Nitro‐L‐arginine (L‐NOARG) persistently increased tone (blocked by L‐arginine) in muscle strips despite blockade of nerve function. Nifedipine prevented or abolished L‐NOARG‐induced, but not carbachol‐induced, contraction showing that tone increase by L‐NOARG required functional L‐Ca channels. Membrane‐bound, myogenic NOS in canine LOS may release NO continuously when Ca2+ entry through L‐Ca channels occurs under physiological conditions and thereby modulate tone in LOS. British Journal of Pharmacology (1998) 123, 1055–1064; doi:10.1038/sj.bjp.0701701